The normal structure of the oral mucosa is maintained by continuous cell proliferation of the epithelium. For some other tissues there is evidence that only a small fraction of the proliferation cells, stem cells, have the ability to proliferate indefinately. It is postulated that these cells provide cells, committed to differentiation, which maintain differentiated tissue mass by a series of augmentation divisions. They are the cells which restore stable structure after epithelial damage. Work so far undertaken indicates the existence of slowly-cycling basal keratinocytes which have patterns of behavior (in vivo and in vitro) suggestive of a function as stem cells. To further investigate the existence of stem cells, the proposed research will use cell labeling and autoradiography to examine the existence of augmentation division in epithelia. The clonal origin of units of epithelial structure will be investigated using chimeric (chick/mouse) skin grown following transplantation to immunodeficient mice. Using the labeling technique developed to identify slowly-cycling cells, the radiosensitivity of putative stem cells, their role in tissue regeneration, and their response to promotors of carcinogenesis will be examined. Histochemical and cell labeling methods will be employed to examine the kinetics of Langerhans cells, another intraepithelial population of slowly-cycling cells.